Miscellaneous Drugs

Question 1

What is the predominant type of alpha receptor in the periphery?
• what GPCR types are specific to each of these pathways?

Answer 1

Periphery:
• Alpha-1 receptors dominate in the periphery with a small amount of Alpha-2

GPCR:
• Gq - used by Alpha-1 because it is a stimulatory Pathway
• Gi - used by Alpha-1 because it is an inhibitory Pathway

Question 2

What is the primary place that Methyldopa, Clonidine, and Guanfacine work?

Answer 2

Vasomotor Center of the brain

Question 3

What is generally the only time you see the activity of alpha-2 receptors in the periphery?

Answer 3

• Local Agonist administration through IV injection or Very High oral doses

Question 4

An alpha-2 receptor is given orally.
• where would it tend to act?
• What would it do?

Answer 4

Oral Alpha-2
•Central effects predominate

Effects:
• Inhibition of Sympathetic Tone
• Reduced Blood Pressure

Question 5

T or F: alpha-2 agonists would be useful in the treatment of hypertension.

Answer 5

True, their central effects make this possible

Question 6

What are the alpha-2 agonists?

Answer 6

• Clonidine

* Guanfacine

Question 7

What are the alpha-2 agonist prodrugs?

Answer 7

• Methyldopa

Question 8

What drugs act in NE storage depletion?

Answer 8

• Reserpirine

* Metyrosine

Question 9

T or F: as many as 30% of essential HTN patients have a primary neurogenic stimulus contributing to the condition.

Answer 9

True, the close link between the sympathetic nervous system means drugs that act on the sympathetic system might be useful in treating HTN

Question 10

What is the role of alpha-2 receptors at rest?

Answer 10

• Limit release of NE from sympathetic nerves

* Limit release of E from chromaffin cells at rest

Question 11

What is the role of alpha-2 heteroreceptors in non-adrenergic neurons?

Answer 11

• Bradycardia and Hypotension via VAGAL ACTIVATION
• Analgesia
• Sedation
• Hypothermia
• Anesthetic-Sparing Effect

Question 12

What is the clinical effect of the alpha-2 agonists and alpha-2 agonist pro-drugs?
• Name them.

Answer 12

Alpha-2 agonist:
• Clonidine
• Guanfacine
• Methyldopa (prodrug)

Effect: 
Loss of Sympathetic Nervous System Tone causing…
• LOWERED Peripheral Vascular Resistance
• LOWERED systolic AND diastolic BP 
• NO reflex tachycardia 
• NO change in Cardiac Output  
• LOWERED plasma renin

Question 13

How does tolerance arise to the alpha-2 agonists?

Answer 13

Less Alpha-2 Receptor on the Cell Surface by:
• Decreased Alpha-2 receptor being made
• More is degraded

Question 14

If you gave someone a vasodilator, what side effect might they experience that could be attenuated by giving a alpha-2 agonist?
• Name them.

Answer 14

•alpha-2 agonist - Blocks Reflex Tachycardia

• Clonidine
• Guanfacine
• Methyldopa (prodrug)

Question 15

T or F: alpha-2 agonists are safe to administer to diabetics and asthmatics.

Answer 15

TRUE

Question 16

What is the method of administration for the alpha-2 agonists?

Answer 16

• Methyldopa (prodrug) - IV
• Clonidine - Transdermal Patch
• Guanfacine - Oral

Question 17

What unique features separate Clonidine and Methyldopa from Guanfacine?

Answer 17

Clonidine:
• patch takes 1-2 days to reach peak effect

Methyldopa:
• needs to be DOSE ADJUSTED in RENAL FAILURE
• Chelated by Concurrent Iron Supplements

Question 18

What are the most common adverse effects of alpha-2 agonists?
• Contraindicated with what disease?
• Name them.

Answer 18

• Drowsines (somnolence)
• Dry Mouth
• Sometimes decreased libido and Impotence

Contraindicated in people with PHEOCHROMOCYTOMA

Drugs:
•Methyl Dopa
• Clonidine
• Guanfacine

Question 19

Which of the alpha-2 agonists might you use to treat pre-eclampsia (malignant HTN in pregnancy)?

Answer 19

Methyl Dopa - has been shown to be safe in pregnant women

Question 20

Reserpine

• MOA

Answer 20

MOA:
• Binds to Adrenergic Storage Vesicles in central AND peripheral adrenergic neurons
• Inhibits Vesicular Catecholamine Transporter VMAT2

Overall, leads to a loss in ability to store and concentrate dopamine

Question 21

Reserpine

• Net effect

Answer 21

• Pharmacological Sympathectomy - Catecholamines just leak out into the cytoplasm and get metabolized to completely inactive molecules
• BOTH CENTRAL and PERIPHERAL depletion of Cats leads to ANTIHYPERTENSIVE EFFECTS

Question 22

T or F: like methyldopa, Reserpine is safe during pregnancy.

Answer 22

False, Reserpine is recognized as a teratogen

**Breastfeeding is even Toxic with Reserpine

Question 23

What are the most common adverse effects of Reserpine?

Answer 23

CNS toxicity
• Inability to concentrate or perform complex tasks

Pyschotic Depression => suicidal Idealtion
• May last several months even after stopping the drug

Exacerbation of Ulcerative Colitis

Teratogen

Question 24

Metyrosine
• MOA
• Treatment

Answer 24

MOA:
• Inhibits the rate limiting step of catecholamine synthesis

Treatment:
• Pheochromocytoma